Hi I'm Abbey. I go to the Bay School of San Francisco and I'm going to be a senior. I love genetics -- mostly Mendelian and Quantitative -- and I am also really interested in bioethics. My mom works for a biotech company, Genentech, which has provided really cool opportunities such as lab visits and research interning that got me more interested in biotechnology. In addition, I'm a type 1 diabetic, which gives me even more reason to learn more about gene therapy and other biological solutions to genetic diseases. As of now, I'm planning on going to nursing school and later specializing in either genetics or anesthesia.
Ethics Proposal: How Genentech could handle incidental findings in clinical trials and data identification
In this proposal, I have outlined how biotech company Genentech could use their new partners 23andMe to handle two prominent ethical issues in their clinical trials: re-identifying participants and incidental findings (IFs).
The Problem: My mom works as the Vice President of Human Resources in Global Product Development at Genentech. Although she isn’t a scientist, she still comes home from work talking about fascinating programs at Genentech, which always peak my interest. Sometimes, she will also ask me my opinion on a topic of debate involving her work, because her team is constantly trying to incorporate how Genentech’s next generation will think. One of these conversations grabbed my attention and I haven’t stopped thinking about is since. My mom explained that Genentech owns the patient data for clinical trial outputs. That data in combination with other information on the patient’s family health history, lifestyle habits can be used to generate insights about other potential diseases besides the condition for which the patient is enrolled in a clinical trial. While the patient outcomes post trial are shared with the participant post-trial there is not a mechanism in the informed consent patient enrollment agreement to share any other learnings - such as those related to DNA sequencing.Further, the data is made anonymous during the clinical trials to protect patient identity and so as not to compromise the results of the trial. This means if Genentech wants to share additional data with the patient post-trial, a way to re-identify the data to give it back to the patient is required and further, Genentech needs to understand if a patient even wants to know other information?. Genentech needs a plan to handle incidental findings (IFs).
Background: Based in San Francisco, “Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. It is among the world's leading biotech companies, with multiple products on the market and a promising development pipeline” (Genentech). On January 6th, 2015, Genentech announced their $10 million deal with 23andMe, a personal genetics company. Their partnership aims to research the genetics behind Parkinson’s by utilizing 23andMe’s participant DNA-bank with sequenced DNA for over two million customers.
Purpose: Genentech has always been a pioneer in the field of synthetic biology (recombinant DNA). Being able to address the issue of Incidental Findings in an efficient, cost-effective and consistent manner, could help lead the way for other biotech companies and transform how medicines are developed. I propose opening a new branch of 23andMe as a third party expert that would initially work with Genentech exclusively to help identify patients and manage communication of IFs. I believe my design can help Genentech and the general biotech industry ethically continue working on clinical trials while keeping a patient-centric focus and improving healthy outcomes for society.
The Idea:__ My plan to solve the problem of re-identification and IF disclosure must adhere to the following criteria to be successful:
Create an unaffiliated group to be the middleman between clinical trial patients and the company (Genentech) running the trial
Create a patient identification program run by the unaffiliated group
Must honor pre-existing patient confidentiality policy for clinical trials at Genentech
Define an IF policy
BLACK BOX GOAL: Maintain this project at a low cost (define budget later)
I would propose that Genentech helps fund a new branch of 23andMe called Team23 that would work with Genentech’s clinical trials.
Patient Re-identification: The existing partnership between Genentech and 23andMe, as well as 23andMe’s existing database and health data analytics technology are ideal assets to help solve this problem. Team23 would maintain a clinical trial database with all of Genentech’s patients. In this database, patients names and anonymized profiles are recorded and assigned a unique number that serves as their identification in the clinical trial. While Team23 employees would have access to a patient’s name, Genentech employees would only have access to the identification number and the anonymized profiles. Both Team23 and Genentech employees would have access to the IFs and sequenced DNA portion. If we think about this like a spreadsheet, the full spreadsheet would contain the following data:
Female, age 48. Trial: Anti-Tau: Alzheimer’s disease: RG6100 is an investigational medicine being evaluated for the potential treatment of Alzheimer’s disease. Target: Tau: This molecule is being developed in collaboration with AC Immune SA.
IF: Craniopharyngioma (brain tumor)
*Possible numbers: 2,176,782,336 We have 6 digit/letter spaces to fill with letters and numbers. This means with 26 letters, and 10 numbers, there are 36 possible choices to fill each space. This can be represented as 363636363636 = 366 = 2,176,782,336 This gives plenty of options for identification numbers to be used.
Female, age 48. Trial: Anti-Tau: Alzheimer’s disease: RG6100 is an investigational medicine being evaluated for the potential treatment of Alzheimer’s disease. Target: Tau: This molecule is being developed in collaboration with AC Immune SA.
IF: Craniopharyngioma (brain tumor)
A Genentech Employee would see:
Name and Contact
Patient Number
Anonymized Profile
Incidental Findings (IFs) and Sequenced DNA
xxxxxxxx
A45G2YHZ
Female, age 48. Trial: Anti-Tau: Alzheimer’s disease: RG6100 is an investigational medicine being evaluated for the potential treatment of Alzheimer’s disease. Target: Tau: This molecule is being developed in collaboration with AC Immune SA.
IF: Craniopharyngioma (brain tumor)
This method ensures that patient confidentiality is respected for trial monitoring processes, but if an IF comes up, or if patient's request to see their analyzed DNA sequencing, the information can be relayed through Team23 who would then be able to reach out to the patient.
A strict policy must be enforced that all IFs are reported, and analyzed, and that all sequenced DNA is submitted and stored in the Team23 database. Note that in the IF policy section, patients who may not want to know about IFs at first can, given this framework, also change their mind. Having all patient data stored with Team23, ensures that it is protected, and can be accessed at any time if desired.
The IF Policy: IFs have become quite controversial in bioethics, and many questions arise: General:
Who should govern the handling of IFs? (“Incidental”)
What rules and guidelines need to be put in place? (“Incidental”)
What should the time frame be for submitting and disclosing an IF? (“Incidental”)
What kinds of IFs should a researcher be aware of/ consider? (“Incidental”)
Follow Ups:
Should all IFs require follow up? If not, what types should? (“Incidental”)
Who pays for follow ups of an IF? (Ofri)
How will clinical validation be done and who will pay for it? (“UBC”)
Should we make higher quality scans in the case of an incidental finding? (Bunnik)
What happens if the clinical validation tests are actually wrong? (Ofri)
What happens if the results show something unexpected (ie. a chromosomal sex that is different than the person’s known sex or different parental lineage)? (Ofri)
Who would be involved in a clinical follow up including contacts at the clinical service point? (“UBC”)
Patient Care:
Are researchers responsible for providing care for a patient with an IF? (Ofri)
Can there be malpractice implications for researchers who are M.D.s? (Ofri)
How will the researcher determine whether an incidental finding is 'actionable' either in terms of future health risks and or treatment? (“UBC”)
Does the company have an ethical obligation to make a referral for treatment? (Ofri)
Disclosure of IFs:
Does the company have an ethical obligation to inform family members who might also be at risk? (Ofri)
How will the possibility of incidental findings be covered with the participant in the consent process? (“UBC”)
How and who would disclose an actionable incidental finding to the participant and or relative (if applicable)? (“UBC”)
This is a lot of uncertainty that needs to be cleared up in the process, but trying to answer just one question at a time will not efficiently bring us to my conclusions. The most important thing about IFs and the disclosure debate in clinical trials is that it is the patient’s choice what they want to know.. By building off of this principle, we can create an IF policy that will actually answer most -- if not all -- of these questions. One study involved interviewing clinical trial patients in the Individual Medicine program at the Mayo Clinic and their loved ones about IFs to help determine what choices a patient needs to make about disclosure. They often noted the importance of deciding for themselves what information was disclosed: “‘I think this is the Individual Medicine program for a reason. Everything has to be on a case by case by case basis because this is serious information and there are many patients who could not handle that information. […] I think the patient should always have the choice under the proper instruction of a medical geneticist. I would never want someone else to decide that for me’ (Dx20yF)”; “‘I absolutely believe this is all about choice. […] It has potential to be a great choice, but yet it may tell me more than I am comfortable knowing right now. So I think it is absolutely a choice and it is all about the choice, but it doesn't mean it is an easy choice’ (Husband of O34yF)”; “‘You feel like if there is information out there that somebody finds out about your genes, you should have the right to know it, right? You should have the choice because it is yours’ (Mother of Dx6yM)” (Clift). This patient-oriented approach aligns with Genentech’s ideals around a patient-centric type of care.
At the beginning of a patient’s clinical trial journey, they go through a consent process. Of course, this involves medical consent in regard to the treatment. In this process, I proposed to include questions that would solve a lot of problems when it comes to IFs. In order to do this, we need to be open about the fact that some people have different beliefs than us, which may influence their decision whether or not to have sequencing and IFs disclosed. The aforementioned study found that some didn’t want to know the results of an IF or sequencing with results unrelated to their current condition and trial due to religious reasoning, it being a burden of knowledge, or having future repercussions (Clift). On the other hand, some did want to know these results because they thought they could help improve quality of life, help prevent or prepare for future health issues, help make informed decisions about current medical treatment, help in more research studies, provide information for family members, or aide in the search for answers about difficult conditions and how to live with them (Clift). Both thought paths are completely acceptable, but I believe patients must be fully aware that not disclosing an IF or sequencing result could lead to unadvised harm, but that in the end it still is their decision. Below is a table of questions I believe should be answered by the patient before they begin a clinical trial in addition to any information needed by researchers in order to complete such trial:
Number
Question
Reasoning
1
Minors (people under 18 years old) must have a legal parent/guardian complete the questions below. ☐ I am a legal parent/guardian; the patient is a minor. ☐ I am over 18 years of age and will complete the questions on my own.
Confirming the patient or parent/guardian is a legal adult.
2
Do you understand that an IF and sequencing results may take many months or even years to be discovered? ☐ Yes, I understand. ☐ No
Informing that trials, sequencing, and IFs can have a long process.
3
In the case that an IF is discovered, do you want to be notified? ☐ Yes, and I know I can change my mind at any time. ☐ No, and I know I can change my mind at any time.
Main disclosure decision.
3a
If YES, I understand that sometimes results from IFs are shocking. They may reveal a serious or even fatal health issue that could change my life. ☐ Yes, I understand. ☐ No, I do not understand.
Noting the severity of some IFs so the patient is aware.
3b
If YES, I want the results to be shared with me… ☐ as soon as they are discovered. ☐ not until after _/_/_(mm/dd/yyyy)
Allowing the patient to decide when they would like to be notified.
4
In the event that an IF or sequencing results are found after I die ☐ I do not want my next of kin to be notified. ☐ I do want my next of kin to be notified. Name (Last, First): Phone: () - *Please speak to a Team23 genetic counselor to add more than 1 contact in this field.
Handling of patient data in the worst case scenario, and others who may be at risk.
5
I understand that all IFs and DNA sequencing results will be stored in the Team23 database. ☐ Yes, I understand. ☐ No, I do not understand.
Noting that no data will be sold to other companies and will be protected in this database and the patient has access to it at their leisure.
5a
I consent to Team23 adding my DNA sequencing to the database at 23andMe in order to use my genetic data in research conducted by Genentech or 23andMe-affiliated research projects. I know that by consenting I will also receive a free 23andMe account where I will have access to 23andMe’s services and my genetic data from DNA sequencing. ☐ I consent. ☐ I do not consent.
Possible consent to allow the patient’s sequencing data to be added to the 23andMe database and using it for other research.
6
I understand that IFs are very common and that Team23 offers one free genetic counseling session for Genentech patients that have any type of IF during a Genentech clinical trial. This free session expires exactly two years after the my information is disclosed to me and I am not required to use it if I do not want to. It can be redeemed at any time, but I know that Genentech and Team23 recommend that I redeem this session sooner than later. I also understand that I can continue genetic counseling with Team23 if I want too, but after my first session which is free, I need to pay for all other appointments. I also understand that if I do not want to speak with a genetic counselor at Team23, I can ask to be referred somewhere else and Team23 will supply me with those referrals within 48 hours of my request. ☐ Yes, I understand. ☐ No, I do not understand.
Clearly stating Genentech’s responsibility to offer genetic counseling and referrals in the case of an IF, and the disclosure timeline.
6a
I understand that I am allowed to bring up to 2 close friends or family members to an IF follow up session at Team23 if I want to. If I am younger than 18, the same applies, but one of those people must be my legal parent/guardian. ☐ Yes, I understand. ☐ No, I do not understand.
Details to maintain efficiency and quality genetic counselling at the Team23 practice.
7
I understand that Team23 will validate the IF before contacting me and will do so in a timely manner. If validation requires the opinion of a medical professional not employed at Team23, they will seek out one of those people before confirming validation of the IF and disclosing that information to me. ☐ Yes, I understand. ☐ No, I do not understand.
Noting responsibility of Team23 to validate an IF before disclosure, so as not to worry the patient.
7a
I understand that interpretation of data is subject to error and that the diagnosis of an IF --though very unlikely-- could be wrong. In this event, I will not hold Genentech or Team23 accountable in any form. I do know that I have been offered a free session with Team23 to help me understand why an interpretation error was made. This complimentary session does not expire and is in addition to a first free session all IF patients are offered. ☐ Yes, I understand. ☐ No, I do not understand.
Giving an understanding of options in case if a mistake on Team23’s part in order to protect the organization from related malpractice.
In addition to these questions, a set of guidelines can be used to help answer even more of the questions:
IF suspicions/concerns/predictions by researchers should be submitted within 24 hours of discovery. Team23 has a 14 day period from the time of submission to validate the IF, and if the patient would like to know, the validated information should be disclosed no later than 15 days after the submission is made.
Researchers should be ‘aware of their surroundings’ meaning they should have general knowledge on the area of the body they are studying. It is not a researcher’s job to constantly aiming to find abnormalities that result in an IF, but they should be educated enough so that if an abnormality presented itself, they could recognize that it was in fact not normal. Researchers must report all suspicious abnormalities to the Team23 database, where Team23 will then validate or reject the IF.
Researchers need to focus on research. They are not responsible for the patient’s care if an IF is found. Team23 is responsible for validating an IF and offering genetic counseling and/or referrals.
Malpractice conflicts are always a possibility. However, Team23 does not condone any illegal actions or those that indicate malpractice in the medical field.
During the validation process within Team23, employees may or may not discover whether or not the IF is actionable. However, Team23 counselors with enough information may suggest treatment options, but the patient still is the ultimate decisionmaker.
After examining the condition of a specific IF or DNA sequencing, counselors at Team23 offer 1 free counselling session to talk through results. This free session expires exactly two years after data disclosure. After that, or if the patient wishes to seek other professional help, Team23 will provide patients with specific referrals for their individual case. Otherwise, patients can stay on with Team23’s doctors (though they are responsible for all payments): genetic counselors, a neurologist, radiologist, oncologist, general surgeon, cardiologist, otolaryngologist (ENT), gastrointestinologist, and psychologist.
Clinical trial patients can request a Team23 counselor to go through the IF policy over the phone or in person at the Team23 clinic (if able). Additionally, all clinical trial patients must verbally consent that they understand what an IF is and that they have filled out the IF policy over the phone with a Team23 employee.
Team23 genetic counselors are responsible for disclosing an IF to a patient/relative (if applicable)
Now we are left with just one question out of the 18 we started with: Does the company have an ethical obligation to inform family members who might also be at risk? Keep in mind that one cannot consent until 18 years old. Additionally, people who could be at risk may be children, siblings, or parents. I have listened to my peers ideas and debated my own for a few hours, yet we cannot come to a conclusion about this ethical issue. Generally we can consider that the patient either will or will not want to hear about their own IFs, and that decision is made in the consent process. Of course, we could add a similar policy form for family who may be at risk and are over 18 years old so that they can decide if an IF is found in the patient whether or not they want to know about their own risk. However, many genetic disorders are most prevalent in the relationship between children and their parents. If there is an IF found in a minor, and their parent may be at risk, of course, the parent is able to make their decision about disclosure. However, if it is the other way around and an IF in the parent puts the minor at risk, what do you do? The minor cannot make their decision until they turn 18, so we could wait until the child turns 18 and then give them the policy form. The problem here is that some genetic conditions would not give a child enough time to turn 18 and be able to decide. For example, imagine a mother is in a clinical trial and researchers find a cancerous gene that is hereditary, and this patient has a seven year old child. This child could already have a cancerous tumor and not know it, and they may not live until they turn 18 to decide about disclosure. In this example, the child’s parent (or guardian) is making the decision about disclosure. If the mother has decided not to have data disclosed, the child may suffer more than if the data was disclosed. So, the parents decide to verify the risk or to reject the possibility of the risk. If the parent decides not to have risk disclosed and validated and as a result the child dies, is Team23 responsible for that child’s death? For not stepping in and trying to save the child’s life? This is one of the messiest ethical issues that arise from IFs.
Materials: For this project to be successful, we need a variety of resources.
Employees: The employees at Team23 involve multiple departments. First the Genetic Counselling Team, which would be made up of genetic counselors who would work full-time at Team23. They would be responsible for speaking to patients about the IF policy or meeting with them, disclosing IFs to patients, offering IF treatment options, and giving referrals. The Specialty Team would be made up of practicing medical professionals who would work part time at the Team23 private practice. This group would include a neurologist, oncologist, radiologist, general surgeon, physician, cardiologist, otolaryngologist (ENT), gastrointestinologist, and psychologist. This group would only be required to come into the practice 2-3 times per week based on their patient’s needs. This group would be supported by the Nursing Team who work full time at the Team23 practice. The Administrative Team would have varying responsibilities from checking patients in and answering phones, to calling patients for the verbal IF policy consent, to ordering office and clinic supplies, to handling patient billing. Liaisons would represent Team23 and Genentech to handle affiliated issues regarding each organization and HR decision-making and policies.
Location: Team23 should be in the Bay Area, given Genentech and 23andMe are headquartered there. The organization would need a space to accommodate the multiple areas of work they would do: one area for the private practice housing the Specialty Team and the Nursing Team with both exam rooms and meeting rooms for them to meet with patients; another area for the Genetic Counselling Team with more comfortable meeting rooms; another area for administrative/clerical support with a private lounge area for all employees; an interactive lobby/ waiting room where patients check in and can learn more about genetics and biotechnology; a research library with multimedia outlets to for employees to learn about genetic disorders and document them, as well as any IFs. The size of this main space would correlate to occupancy ratios in buildings based the number of people to the square foot ratio.
Funding: I am not sure how much funding would be needed to complete this project, but the hope would be to keep costs as low as possible. I would approach this as a start up/ pilot organization and would need to find a Not for Profit Government and Private Business Investor to partner if Genentech and 23andMe could not pay for it on their own. The benefit of this approach is that if successful, it could yield benefits much beyond Genentech and 23andMe.
Advantages: My solution offers ethical and practical solutions that create mutual benefits for Genentech, 23andMe, and patients. The mission of 23andMe is “to help people access, understand and benefit from the human genome” (“Our Mission”). This solution not only helps clinical trial patients have the opportunity to do just that, but also use genomic information to improve their quality of life. Additionally, the 23andMe website states that “on average, one individual contributed to 200 different research studies” (“Our Mission”). Adding more people to their database means there is more information for researchers to develop more clinical trials and cure diseases. Genentech’s mission is as follows: “We believe it’s urgent to deliver medical solutions right now – even as we develop innovations for the future. We are passionate about transforming patients’ lives. We are courageous in both decision and action. And we believe that good business means a better world. That is why we come to work each day. We commit ourselves to scientific rigor, unassailable ethics, and access to medical innovations for all. We do this today to build a better tomorrow. We are proud of who we are, what we do, and how we do it. We are many, working as one across functions, across companies, and across the world” (Genentech) I believe my solution embodies both mission statements. Offering genetic information to patients sooner than later can help them avoid further complications, giving them what they will need later, and hopefully changing the life of patients and families for the better. This idea involves making some hard decisions and acting upon them will take courage from both companies and patients. . The proposal to offer free services (23andMe access and an appointment to discuss an IF with a Team23 genetic counselor) so that all patients can access expertise also involves a substantial investment by the companies. Overall, this proposal involves furthering the beneficial collaboration between two business partners dedicated to transforming healthcare for society.
Presentation Link in Google Slides: Here
Ethics Proposal:
How Genentech could handle incidental findings in clinical trials and data identification
In this proposal, I have outlined how biotech company Genentech could use their new partners 23andMe to handle two prominent ethical issues in their clinical trials: re-identifying participants and incidental findings (IFs).
The Problem:
My mom works as the Vice President of Human Resources in Global Product Development at Genentech. Although she isn’t a scientist, she still comes home from work talking about fascinating programs at Genentech, which always peak my interest. Sometimes, she will also ask me my opinion on a topic of debate involving her work, because her team is constantly trying to incorporate how Genentech’s next generation will think. One of these conversations grabbed my attention and I haven’t stopped thinking about is since. My mom explained that Genentech owns the patient data for clinical trial outputs. That data in combination with other information on the patient’s family health history, lifestyle habits can be used to generate insights about other potential diseases besides the condition for which the patient is enrolled in a clinical trial. While the patient outcomes post trial are shared with the participant post-trial there is not a mechanism in the informed consent patient enrollment agreement to share any other learnings - such as those related to DNA sequencing.Further, the data is made anonymous during the clinical trials to protect patient identity and so as not to compromise the results of the trial. This means if Genentech wants to share additional data with the patient post-trial, a way to re-identify the data to give it back to the patient is required and further, Genentech needs to understand if a patient even wants to know other information?. Genentech needs a plan to handle incidental findings (IFs).
Background:
Based in San Francisco, “Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious or life-threatening medical conditions. It is among the world's leading biotech companies, with multiple products on the market and a promising development pipeline” (Genentech). On January 6th, 2015, Genentech announced their $10 million deal with 23andMe, a personal genetics company. Their partnership aims to research the genetics behind Parkinson’s by utilizing 23andMe’s participant DNA-bank with sequenced DNA for over two million customers.
Purpose:
Genentech has always been a pioneer in the field of synthetic biology (recombinant DNA). Being able to address the issue of Incidental Findings in an efficient, cost-effective and consistent manner, could help lead the way for other biotech companies and transform how medicines are developed. I propose opening a new branch of 23andMe as a third party expert that would initially work with Genentech exclusively to help identify patients and manage communication of IFs. I believe my design can help Genentech and the general biotech industry ethically continue working on clinical trials while keeping a patient-centric focus and improving healthy outcomes for society.
The Idea:__
My plan to solve the problem of re-identification and IF disclosure must adhere to the following criteria to be successful:
- Create an unaffiliated group to be the middleman between clinical trial patients and the company (Genentech) running the trial
- Create a patient identification program run by the unaffiliated group
- Must honor pre-existing patient confidentiality policy for clinical trials at Genentech
- Define an IF policy
- BLACK BOX GOAL: Maintain this project at a low cost (define budget later)
I would propose that Genentech helps fund a new branch of 23andMe called Team23 that would work with Genentech’s clinical trials.Patient Re-identification:
The existing partnership between Genentech and 23andMe, as well as 23andMe’s existing database and health data analytics technology are ideal assets to help solve this problem. Team23 would maintain a clinical trial database with all of Genentech’s patients. In this database, patients names and anonymized profiles are recorded and assigned a unique number that serves as their identification in the clinical trial. While Team23 employees would have access to a patient’s name, Genentech employees would only have access to the identification number and the anonymized profiles. Both Team23 and Genentech employees would have access to the IFs and sequenced DNA portion. If we think about this like a spreadsheet, the full spreadsheet would contain the following data:
(123) 456-7890
msmith@gmail.com
Trial: Anti-Tau: Alzheimer’s disease: RG6100 is an investigational medicine being evaluated for the potential treatment of Alzheimer’s disease.
Target: Tau: This molecule is being developed in collaboration with AC Immune SA.
We have 6 digit/letter spaces to fill with letters and numbers. This means with 26 letters, and 10 numbers, there are 36 possible choices to fill each space. This can be represented as 363636363636 = 366 = 2,176,782,336
This gives plenty of options for identification numbers to be used.
A Team23 employee would see:
(123) 456-7890
msmith@gmail.com
Trial: Anti-Tau: Alzheimer’s disease: RG6100 is an investigational medicine being evaluated for the potential treatment of Alzheimer’s disease.
Target: Tau: This molecule is being developed in collaboration with AC Immune SA.
A Genentech Employee would see:
Trial: Anti-Tau: Alzheimer’s disease: RG6100 is an investigational medicine being evaluated for the potential treatment of Alzheimer’s disease.
Target: Tau: This molecule is being developed in collaboration with AC Immune SA.
This method ensures that patient confidentiality is respected for trial monitoring processes, but if an IF comes up, or if patient's request to see their analyzed DNA sequencing, the information can be relayed through Team23 who would then be able to reach out to the patient.
A strict policy must be enforced that all IFs are reported, and analyzed, and that all sequenced DNA is submitted and stored in the Team23 database. Note that in the IF policy section, patients who may not want to know about IFs at first can, given this framework, also change their mind. Having all patient data stored with Team23, ensures that it is protected, and can be accessed at any time if desired.
The IF Policy:
IFs have become quite controversial in bioethics, and many questions arise:
General:
- Who should govern the handling of IFs? (“Incidental”)
- What rules and guidelines need to be put in place? (“Incidental”)
- What should the time frame be for submitting and disclosing an IF? (“Incidental”)
- What kinds of IFs should a researcher be aware of/ consider? (“Incidental”)
Follow Ups:- Should all IFs require follow up? If not, what types should? (“Incidental”)
- Who pays for follow ups of an IF? (Ofri)
- How will clinical validation be done and who will pay for it? (“UBC”)
- Should we make higher quality scans in the case of an incidental finding? (Bunnik)
- What happens if the clinical validation tests are actually wrong? (Ofri)
- What happens if the results show something unexpected (ie. a chromosomal sex that is different than the person’s known sex or different parental lineage)? (Ofri)
- Who would be involved in a clinical follow up including contacts at the clinical service point? (“UBC”)
Patient Care:- Are researchers responsible for providing care for a patient with an IF? (Ofri)
- Can there be malpractice implications for researchers who are M.D.s? (Ofri)
- How will the researcher determine whether an incidental finding is 'actionable' either in terms of future health risks and or treatment? (“UBC”)
- Does the company have an ethical obligation to make a referral for treatment? (Ofri)
Disclosure of IFs:This is a lot of uncertainty that needs to be cleared up in the process, but trying to answer just one question at a time will not efficiently bring us to my conclusions. The most important thing about IFs and the disclosure debate in clinical trials is that it is the patient’s choice what they want to know.. By building off of this principle, we can create an IF policy that will actually answer most -- if not all -- of these questions. One study involved interviewing clinical trial patients in the Individual Medicine program at the Mayo Clinic and their loved ones about IFs to help determine what choices a patient needs to make about disclosure. They often noted the importance of deciding for themselves what information was disclosed: “‘I think this is the Individual Medicine program for a reason. Everything has to be on a case by case by case basis because this is serious information and there are many patients who could not handle that information. […] I think the patient should always have the choice under the proper instruction of a medical geneticist. I would never want someone else to decide that for me’ (Dx20yF)”; “‘I absolutely believe this is all about choice. […] It has potential to be a great choice, but yet it may tell me more than I am comfortable knowing right now. So I think it is absolutely a choice and it is all about the choice, but it doesn't mean it is an easy choice’ (Husband of O34yF)”; “‘You feel like if there is information out there that somebody finds out about your genes, you should have the right to know it, right? You should have the choice because it is yours’ (Mother of Dx6yM)” (Clift). This patient-oriented approach aligns with Genentech’s ideals around a patient-centric type of care.
At the beginning of a patient’s clinical trial journey, they go through a consent process. Of course, this involves medical consent in regard to the treatment. In this process, I proposed to include questions that would solve a lot of problems when it comes to IFs. In order to do this, we need to be open about the fact that some people have different beliefs than us, which may influence their decision whether or not to have sequencing and IFs disclosed. The aforementioned study found that some didn’t want to know the results of an IF or sequencing with results unrelated to their current condition and trial due to religious reasoning, it being a burden of knowledge, or having future repercussions (Clift). On the other hand, some did want to know these results because they thought they could help improve quality of life, help prevent or prepare for future health issues, help make informed decisions about current medical treatment, help in more research studies, provide information for family members, or aide in the search for answers about difficult conditions and how to live with them (Clift). Both thought paths are completely acceptable, but I believe patients must be fully aware that not disclosing an IF or sequencing result could lead to unadvised harm, but that in the end it still is their decision.
Below is a table of questions I believe should be answered by the patient before they begin a clinical trial in addition to any information needed by researchers in order to complete such trial:
☐ I am a legal parent/guardian; the patient is a minor.
☐ I am over 18 years of age and will complete the questions on my own.
☐ Yes, I understand.
☐ No
☐ Yes, and I know I can change my mind at any time.
☐ No, and I know I can change my mind at any time.
I understand that sometimes results from IFs are shocking. They may reveal a serious or even fatal health issue that could change my life.
☐ Yes, I understand.
☐ No, I do not understand.
I want the results to be shared with me…
☐ as soon as they are discovered.
☐ not until after _/_/_(mm/dd/yyyy)
☐ I do not want my next of kin to be notified.
☐ I do want my next of kin to be notified.
Name (Last, First):
Phone: () -
*Please speak to a Team23 genetic counselor to add more than 1 contact in this field.
☐ Yes, I understand.
☐ No, I do not understand.
☐ I consent.
☐ I do not consent.
☐ Yes, I understand.
☐ No, I do not understand.
☐ Yes, I understand.
☐ No, I do not understand.
☐ Yes, I understand.
☐ No, I do not understand.
☐ Yes, I understand.
☐ No, I do not understand.
In addition to these questions, a set of guidelines can be used to help answer even more of the questions:
Now we are left with just one question out of the 18 we started with:
Does the company have an ethical obligation to inform family members who might also be at risk? Keep in mind that one cannot consent until 18 years old. Additionally, people who could be at risk may be children, siblings, or parents.
I have listened to my peers ideas and debated my own for a few hours, yet we cannot come to a conclusion about this ethical issue. Generally we can consider that the patient either will or will not want to hear about their own IFs, and that decision is made in the consent process. Of course, we could add a similar policy form for family who may be at risk and are over 18 years old so that they can decide if an IF is found in the patient whether or not they want to know about their own risk. However, many genetic disorders are most prevalent in the relationship between children and their parents. If there is an IF found in a minor, and their parent may be at risk, of course, the parent is able to make their decision about disclosure. However, if it is the other way around and an IF in the parent puts the minor at risk, what do you do? The minor cannot make their decision until they turn 18, so we could wait until the child turns 18 and then give them the policy form. The problem here is that some genetic conditions would not give a child enough time to turn 18 and be able to decide. For example, imagine a mother is in a clinical trial and researchers find a cancerous gene that is hereditary, and this patient has a seven year old child. This child could already have a cancerous tumor and not know it, and they may not live until they turn 18 to decide about disclosure. In this example, the child’s parent (or guardian) is making the decision about disclosure. If the mother has decided not to have data disclosed, the child may suffer more than if the data was disclosed. So, the parents decide to verify the risk or to reject the possibility of the risk. If the parent decides not to have risk disclosed and validated and as a result the child dies, is Team23 responsible for that child’s death? For not stepping in and trying to save the child’s life? This is one of the messiest ethical issues that arise from IFs.
Materials:
For this project to be successful, we need a variety of resources.
Employees: The employees at Team23 involve multiple departments. First the Genetic Counselling Team, which would be made up of genetic counselors who would work full-time at Team23. They would be responsible for speaking to patients about the IF policy or meeting with them, disclosing IFs to patients, offering IF treatment options, and giving referrals. The Specialty Team would be made up of practicing medical professionals who would work part time at the Team23 private practice. This group would include a neurologist, oncologist, radiologist, general surgeon, physician, cardiologist, otolaryngologist (ENT), gastrointestinologist, and psychologist. This group would only be required to come into the practice 2-3 times per week based on their patient’s needs. This group would be supported by the Nursing Team who work full time at the Team23 practice. The Administrative Team would have varying responsibilities from checking patients in and answering phones, to calling patients for the verbal IF policy consent, to ordering office and clinic supplies, to handling patient billing. Liaisons would represent Team23 and Genentech to handle affiliated issues regarding each organization and HR decision-making and policies.
Location: Team23 should be in the Bay Area, given Genentech and 23andMe are headquartered there. The organization would need a space to accommodate the multiple areas of work they would do: one area for the private practice housing the Specialty Team and the Nursing Team with both exam rooms and meeting rooms for them to meet with patients; another area for the Genetic Counselling Team with more comfortable meeting rooms; another area for administrative/clerical support with a private lounge area for all employees; an interactive lobby/ waiting room where patients check in and can learn more about genetics and biotechnology; a research library with multimedia outlets to for employees to learn about genetic disorders and document them, as well as any IFs. The size of this main space would correlate to occupancy ratios in buildings based the number of people to the square foot ratio.
Funding: I am not sure how much funding would be needed to complete this project, but the hope would be to keep costs as low as possible. I would approach this as a start up/ pilot organization and would need to find a Not for Profit Government and Private Business Investor to partner if Genentech and 23andMe could not pay for it on their own. The benefit of this approach is that if successful, it could yield benefits much beyond Genentech and 23andMe.
Advantages:
My solution offers ethical and practical solutions that create mutual benefits for Genentech, 23andMe, and patients. The mission of 23andMe is “to help people access, understand and benefit from the human genome” (“Our Mission”). This solution not only helps clinical trial patients have the opportunity to do just that, but also use genomic information to improve their quality of life. Additionally, the 23andMe website states that “on average, one individual contributed to 200 different research studies” (“Our Mission”). Adding more people to their database means there is more information for researchers to develop more clinical trials and cure diseases. Genentech’s mission is as follows:
“We believe it’s urgent to deliver medical solutions right now – even as we develop innovations for the future. We are passionate about transforming patients’ lives. We are courageous in both decision and action. And we believe that good business means a better world.
That is why we come to work each day. We commit ourselves to scientific rigor, unassailable ethics, and access to medical innovations for all. We do this today to build a better tomorrow.
We are proud of who we are, what we do, and how we do it. We are many, working as one across functions, across companies, and across the world” (Genentech)
I believe my solution embodies both mission statements. Offering genetic information to patients sooner than later can help them avoid further complications, giving them what they will need later, and hopefully changing the life of patients and families for the better. This idea involves making some hard decisions and acting upon them will take courage from both companies and patients. . The proposal to offer free services (23andMe access and an appointment to discuss an IF with a Team23 genetic counselor) so that all patients can access expertise also involves a substantial investment by the companies. Overall, this proposal involves furthering the beneficial collaboration between two business partners dedicated to transforming healthcare for society.